Colorectal Cancer Association of Canada consensus meeting: raising the standards of care for early-stage rectal cancer

The purpose of the meeting reported here was to develop a set of national evidence-based standards for assessing and managing patients with potentially resectable rectal cancer. This report represents the consensus of the multidisciplinary group of Canadian rectal cancer experts attending that meeting.


Purpose
The purpose of the meeting reported here was to develop a set of national evidence-based standards for assessing and managing patients with potentially resectable rectal cancer. This report represents the consensus of the multidisciplinary group of Canadian rectal cancer experts attending that meeting.

Participants
A representative group of Canadian rectal cancer experts from the key disciplines (surgical, medical and radiation oncology, pathology, radiology) involved in managing resectable rectal cancer were invited (Table i).

Target Audience
• Health care professionals involved in the care of patients with potentially curable rectal cancer • Stakeholders (provincial cancer agencies, hospitals, and so on) responsible for program and funding decisions related to the management of potentially resectable cancer • Patient advocacy and education groups such as the Colorectal Cancer Association of Canada

Basis of Recommendations
All recommendations are based on a structured presentation and discussion of the best available evidence.

Application of Recommendations
These standards provide the basis for a discussion with patients regarding management options. Treatment plans will depend on a more complete discussion of the risks and benefits of proposed therapies with individual patients.
Significant progress has been made in improving outcomes for patients with potentially resectable rectal cancer; however, further improvement is necessary. Offering patients the option of participating in clinical trials should be a priority.
Optimally, the approach for assessing and managing patients with rectal cancer should involve a collaborative, multidisciplinary team (including all relevant medical specialties and allied health professionals). For example, optimal rectal cancer management is predicated on open communication and quality assurance between the surgeon and the pathologist describing the extent of disease of the surgical specimen for optimal postsurgical treatment choices.
Radiologic assessment and imaging should be completed within 2-3 weeks to ensure that the appropriate information is available to make timely management decisions.

Question 3
Which neoadjuvant radiation protocol or protocols should be standard when combined with chemotherapy?

Consensus Statement 3
Preoperative neoadjuvant radiotherapy is the standard of care for clinically staged ii and iii patients. Long-course radiation (minimum of 45 cGy over 5 weeks) with fluoropyrimidine chemotherapy or short-course radiation without chemotherapy can be considered. A multidisciplinary team approach (with or without a tumour board) is important to review individual cases and reach consensus on the appropriate course of treatment (short-vs. longcourse radiation).
This statement utilizes Bujko

Question 4
Which neoadjuvant chemotherapy protocol or protocols should be standard when combined with longcourse radiation?

Consensus Statement 4
The optimal fluoropyrimidine-based chemotherapy is based on extrapolation of data from randomized trials of combined-modality chemoradiation used in the postoperative setting. Use fluoropyrimidine-based chemotherapy with long-course radiation. Protracted fluoropyrimidine is preferable to bolus 5-fluorouracil because of improved tolerability and similar efficacy, as seen in the largest and most recent randomized trial (int 0144) 29

Question 5
What should be the surgical standard of care for rectal cancer?

Consensus Statement 5
All stage ii-iii rectal cancers should be considered for neoadjuvant treatment. For all rectal cancers undergoing radical surgery, tme principles must be followed. Surgeons treating rectal cancer patients should be familiar with the tme surgery. Quality should be assured through independent evaluations by the surgeon and the pathologist. Synoptic operative reporting is encouraged.
Trans-anal excision represents an oncologic compromise for most rectal cancer patients. Consider it only in patients with comorbidities, realizing that it requires excellent preoperative assessment and high intraoperative expertise.
Because trans-anal endoscopic microsurgery is a new approach for local excision, patients being treated using this approach should preferably be enrolled in trials or prospective follow-up studies. This

Question 6
What criteria should be standard for handling, evaluating, and reporting on the surgical specimen?

Consensus Statement 6
The surgeon should be aware of the standard macroscopic evaluation (grades 1, 2, 3) of the surgical specimen immediately after removal of the rectum. The pathologist receiving the specimen should also grade the macroscopic quality of the excision, independently of grading by the surgeon. Optimal management is predicated on productive, open communication between the surgeon and the pathologist so that quality assurance and appropriate mechanisms for evaluation and improvement can be achieved (see also consensus statement 5). Collaboration is mandatory for optimal evaluation; that is, margin assessment, surgical difficulty encountered, neoadjuvant treatment given to the patient must be communicated. (For optimal assessment of the specimen, the pathologist has to be informed if neoadjuvant therapy was administered.) This

Question 7
What is the standard adjuvant chemotherapy post neoadjuvant treatment and surgery?

Consensus Statement 7
All patients should be considered for 4-6 months of fluoropyrimidine-based therapy. Based on extrapolation of phase III trials for adjuvant treatment of colon cancer, adjuvant oxaliplatin-based therapy should be considered for patients at high risk for recurrence, including, but not limited to those who are • ypN-positive.

ACKNOWLEDGMENTS
The Colorectal Cancer Association of Canada (ccac) thanks all contributors to this consensus guideline. Of particular note, the ccac thanks Drs. S. Berry, C. Marginean, C. Richard, A. Smith, and T. Vuong, and Shaniah Leduc rn for their contributions to the writing of this paper.

CONFLICTS OF INTEREST
Participants disclosed potential conflicts of interest within the past 2 years:

Mesorectal Envelope
The nonperitonealized surface of the fresh specimen is examined circumferentially, and the completeness of the mesorectum is scored as complete, partially complete, or incomplete 8-10 . The entire specimen is scored according to the worst area.
• Complete: Intact bulky mesorectum with a smooth surface. Only minor irregularities of the mesorectal surface. No surface defects greater than 5 mm in depth. No coning towards the distal margin of the specimen. After transverse sectioning, the circumferential margin appears smooth.
• Nearly complete: Moderate bulk to the mesorectum. Irregularity of the mesorectal surface with defects greater than 5 mm, but none extending to the muscularis propria. No areas of visibility of the muscularis propria except at the insertion site of the levator ani muscles.
• Incomplete: Little bulk to the mesorectum. Defects in the mesorectum down to the muscularis propria. After transverse sectioning, the circumferential margin appears very irregular.

Circumferential (Radial) Margin
In addition to addressing the proximal and distal margins, the circumferential (radial) margin (crm) must be assessed for any segment either unencased or incompletely encased by peritoneum. The crm represents the adventitial soft tissue margin closest to the deepest penetration of tumour and is created surgically by blunt or sharp dissection of the retroperitoneal or subperitoneal aspect respectively. The serosal surface (visceral peritoneum) does not constitute a surgical margin. The distance between the tumour and the crm should be reported. The crm is considered negative if the tumour is more than 1 mm from the inked nonperitonealized surface, but should be recorded as positive if tumour is located 1 mm or less from the nonperitonealized surface. This description includes both tumour within a lymph node and direct tumour extension; however, if crm positivity is based solely on intranodal tumour, this fact should be stated (cap protocol).

Pathologic Tumour Response to Neoadjuvant Therapy (ypN)
The tumour response to neoadjuvant chemoradiation therapy should be recorded at least as present, recording the percentage of fibrosis in respect to residual tumour (or no response identified). The entire scarred area of the rectum has to be blocked and scrutinized meticulously for any foci of residual tumour cells. Acellular mucin pools post neoadjuvant therapy are considered to represent a pathologic complete response. Tumour regression should be assessed only in the primary tumour; lymph node metastases should not be included in the assessment.
Several grading systems for tumour response are available 11,12 . A 3-point system showed good interobserver reproducibility 12 and may be clinically important, but it is not yet validated or regularly used in patient management and is not required for accreditation purposes for the Commission on Cancer.